This project is concerned with the problem of regulatory phenomena during development as exemplified by biochemical aspects of cellular proliferation and differentiation. The functional unit of the intestine comprised of the crypt and the villus has been the primary focus of these studies. In the crypt and other model cellular systems, the metabolic interrelationships of de novo pyrimidine biosynthesis will be studied utilizing measurement of intermediates, enzymes, and the effects of inhibitors of the pathway. The disaccharidases located in the intestinal villus will be utilized as molecular markers of differentiation. In particular, the investigation will concentrate on genetic and biochemical aspects of disaccharidases, the mechanism of transport of these enzymes from the endoplasmic reticulum to the brush border, and the processes involved in the induction of sucrase by steroids. Other environmental factors affecting the activity of sucrase, such as diet, will be examined with immunochemical techniques. The general goals are to locate explicitly the initial appearance of the disaccharidases and to attempt to relate their appearance to the process of cellular proliferation.